Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster

Author(s)

Salminen, Tiina S. ^[1] ; Cannino, Giuseppe ^[1] ; Oliveira, Marcos T. ^[2] ; Lillsunde, Paivi ^[1] ; Jacobs, Howard T. ^{[3, 1]} ; Kaguni, Laurie S. ^{[4, 5, 1]}

Affiliation

^[1] Univ Tampere, Fac Med & Hlth Technol, FI-331014 Tampere - Finland

^[2] Univ Estadual Paulista, Dept Tecnol, Fac Ciencias Agr & Vet, BR-14884900 Jaboticabal, SP - Brazil

^[3] Univ Helsinki, Inst Biotechnol, FI-00014 Helsinki - Finland

^[4] Michigan State Univ, Ctr Mitochondrial Sci & Med, E Lansing, MI 48824 - USA

^[5] Michigan State Univ, Dept Biochem & Mol Biol, 603 Wilson Rd, E Lansing, MI 48824 - USA

• Document type: Journal article
• Source: G3-GENES, GENOMES, GENETICS; v. 9, n. 7, p. 2225-2234, JUL 2019.
• Web of Science Citations: 1

Abstract

Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko(25t) mutation, affecting mitochondrial protein synthesis. When combined with tko(25t), the mtDNA from wild strain KSA2 produced pupal lethality, accompanied by the presence of melanotic nodules in L3 larvae. KSA2 mtDNA, which carries a substitution at a conserved residue of cytochrome b that is predicted to be involved in subunit interactions within respiratory complex III, conferred drastically decreased respiratory capacity and complex III activity in the tko(25t) but not a wild-type nuclear background. The complex III inhibitor antimycin A was able to phenocopy effects of the tko(25t) mutation in the KSA2 mtDNA background. This is the first report of a lethal, nuclear-mitochondrial interaction within a metazoan species, representing a paradigm for understanding genetic interactions between nuclear and mitochondrial genotype relevant to human health and disease. (AU)

• FAPESP's process: 14/02253-6 - Investigating the metabolic alterations caused by the transgenic expression of the mitochondrial alternative oxidase of Ciona intestinalis in Drosophila melanogaster
• Grantee: Marcos Túlio de Oliveira
• Support Opportunities: Research Grants - Young Investigators Grants